Quantum dots and their uses

Abstract

Quantum dots having ligands that comprise tiopronin capping groups are disclosed, along with a method for their preparation. The biocompatibility of these quantum dots is also demonstrated. The functionalization of the quantum dots of the present invention with targeting groups is also described using the example of a translocation peptide that allows the quantum dots to penetrate into the nucleus of cells.

1. A quantum dot comprising a semiconductor core to which a plurality of ligands are covalently linked, wherein the ligands comprise a tiopronin capping group linked to a targeting group, said targeting group directing the quantum dot to a target selected from the group consisting of tissue type, a cell type and a cellular organelle, wherein the targeting group is selected from the group consisting of a translocation signal peptide, a mitochondrial targeting sequence, a nuclear localisation signal, a perioxisomal targeting signal and a transport protein. 
     
     
       2. The quantum dot of  claim 1 , wherein the semiconductor core of the quantum dot is formed from a metal sulphide selected from the group consisting of cadmium sulphide (CdS), zinc sulphide (ZnS) and lead sulphide (PbS). 
     
     
       3. The quantum dot of  claim 1 , wherein the semiconductor core of the quantum dot is formed from CdS. 
     
     
       4. The quantum dot of  claim 3 , wherein the quantum dot emits light at a wavelength between about 400 nm and about 900 nm. 
     
     
       5. The quantum dot of  claim 3 , wherein the quantum dot has an excitation wavelength of between about 250 nm and about 600 nm. 
     
     
       6. The quantum dot of  claim 1 , wherein the mean diameter of the quantum dot is between about 2 nm and about 5 nm. 
     
     
       7. The quantum dot of  claim 1 , wherein the quantum dot is water dispersable. 
     
     
       8. The quantum dot of  claim 1 , wherein tiopronin comprises a thiol group though which the tiopronin capping group is covalently linked to the semiconductor core of the quantum dot via formation of a metal-sulphide bond. 
     
     
       9. The quantum dot of  claim 1  which comprises at least one further species of ligand. 
     
     
       10. The quantum dot of  claim 9 , wherein the further species of ligand is selected from the group consisting of a carbohydrate group, a glycoconjugate, a peptide group, a lipid group, a drug or a prodrug and a nucleic acid molecule. 
     
     
       11. The quantum dot of  claim 9 , wherein the at least one further species of ligand that is covalently linked to the semiconductor core. 
     
     
       12. The quantum dot of  claim 9 , wherein the at least one further species of ligand that is covalently linked to tiopronin group. 
     
     
       13. The quantum dot of  claim 1 , wherein the tiopronin capping group comprises a carboxyl group through which the targeting group is covalently linked via a coupling reaction. 
     
     
       14. The quantum dot of  claim 1 , wherein the targeting group is one member of a specific binding pair. 
     
     
       15. The quantum dot of  claim 1 , wherein the targeting group is a translocation signal peptide. 
     
     
       16. The quantum dot of  claim 15 , wherein the translocation signal peptide is a TAT peptide. 
     
     
       17. A composition comprising a population of quantum dots according to  claim 1 . 
     
     
       18. The composition of  claim 17 , wherein the composition is lyophilized. 
     
     
       19. The composition of  claim 18 , wherein the composition comprising the quantum dots is stable in a lyophilized form for a year when stored in the absence of light at 40C. 
     
     
       20. A method of detecting a component of a biological system, the method comprising:
 (a) providing in the biological system a composition of quantum dots, the quantum dots comprising a semiconductor core to which a plurality of ligands are covalently linked, wherein the ligands comprise a tiopronin capping group linked to a targeting group that is capable of interacting with the component of the biological system; 
 (b) exposing the biological system to radiation at an excitation wavelength of the quantum dots; 
 (c) detecting radiation emitted by the quantum dots at their emission wavelength thereby to detect the component in the biological system, 
 
       wherein the targeting group is a signal group that carries the quantum dot to a component of the biological system, which component is selected from the group consisting of a tissue type, a cell type and a cellular organelle, 
       and wherein the targeting group is selected from the group consisting of a translocation signal peptide, a mitochondrial targeting sequence, a nuclear localisation signal, a perioxisomal targeting sequence and a transport protein. 
     
     
       21. The method of  claim 20 , wherein the biological systems is selected from the group consisting of an in vivo biological system or an in vitro biological system. 
     
     
       22. The method of  claim 20 , wherein the targeting group directly interacts with the component of the biological system. 
     
     
       23. The method of  claim 20 , wherein the translocation signal is a TAT peptide. 
     
     
       24. The method of  claim 20 , wherein the method is for an immunoassay, a hybridization assay, cytometry or imaging. 
     
     
       25. The method of  claim 20 , wherein the method is for diagnosing a disease. 
     
     
       26. A method of labelling a component of a biological system, the method comprising contacting the component of the biological system with a composition of quantum dots, the quantum dots comprising a semiconductor core to which a plurality of ligands are covalently linked, wherein the ligands comprise a tiopronin capping group linked to a targeting group, wherein the targeting group is capable of binding to or associating with the component of the biological system thereby to label it, said component being selected from the group consisting of a tissue type, a cell type and a cellular organelle, wherein the targeting group is selected from the group consisting of a translocation signal peptide, a mitochondrial targeting sequence, a nuclear localization signal, a perioxisomal targeting sequence and a transport protein. 
     
     
       27. A method of making composition of quantum dots comprising metal sulphide cores, wherein the metal sulphide is selected from the group consisting of cadmium sulphide, zinc sulphide and lead sulphide, to which a plurality of ligands are covalently linked, wherein the ligands comprise a tiopronin group, the method comprising mixing sodium sulphate, an aqueous solution of tiopronin and a metal nitrate, wherein the metal nitrate is selected from the group consisting of cadmium nitrate, zinc nitrate and lead nitrate, thereby producing the quantum dots in a self-assembly reaction in which thiol groups of the tiopronin covalently link to the semiconductor cores via metal-sulphide bonds. 
     
     
       28. The method of  claim 27 , wherein the method is single-step procedure. 
     
     
       29. The method of  claim 27 , wherein mixing step is carried out at room temperature. 
     
     
       30. The method of  claim 27 , further comprising coupling a targeting group to the carboxyl group of the tiopronin. 
     
     
       31. The method of  claim 27 , wherein in the coupling step, the carboxyl group of the tiopronin group is coupled to a reactive amine group of the targeting group. 
     
     
       32. The method of  claim 27 , wherein the coupling step is a carbodiimide coupling reaction in the presence of N-[3-(dimethylamino)propyl]-N′-ethylcarbodiimide hydrochloride (EDC), and optionally N-hydroxysuccinimide (NHS).